OBJECTIVE To examine the effects of leptin on LHRH release in vivo. It has been shown that leptin, an obese gene product, is involved in the regulation of LH release. However, the role of leptin in LHRH release in non-human primates is yet to be examined. In this study the effects of leptin on LHRH release in vivo in the stalk-median eminence (S-ME) in ovariectomized rhesus monkeys were studied using a push-pull perfusion method. Modified Krebs-Ringer phosphate buffer (20 5l/min) was infused into the S-ME, while perfusates were continuously collected at 10-min intervals. LHRH in perfusates were measured by RIA. Leptin at 3 doses (0.01, 1, 100 5M) or vehicle was randomly infused for 10 min at 90-min intervals. Results were as follows Leptin significantly increased LHRH release in a dose-dependent manner. Leptin at 100 5M induced an increase in LHRH release Mean LHRH levels were significantly higher (164.7128.7%, p<0.05, n=11) during the 10-min period of leptin infusion as compared to the levels during the 20-min preinfusion period, and this elevation continued for 10 min after leptin infusion. Leptin at 1 5M also induced a significant increase (141.3117.7%, p<0.05, n=16) in LHRH release during the leptin infusion, but subsequently returned to preinfusion levels. Infusion with 0.01 5M leptin stimulated LHRH release during infusion, but the increase was not statistically significant (p<0.1, n=13). Vehicle infusion did not induce any significant changes in LHRH release during or after infusion (n=16). These results suggest that direct infusion of leptin into the S-ME stimulates LHRH release in ovariectomized monkeys. Whether leptin in the S-ME stimulates LHRH release directly or through interneurons, such as neuropeptide-Y neurons, remains to be clarified. FUTURE DIRECTIONS We plan to examine the causal relationship between leptin effects and NPY release. KEY WORDS leptin, pulsatile LHRH release, monkey hypothalamus FUNDING NIH HD15433, HD15433S, & RR00167 PUBLICATIONS Mizuno, M., Kasuya, E., Mogi, K., and Terasawa, E. Leptin stimulates in vivo LHRH release in the stalk-median eminence in adult ovariectomized female rhesus monkeys. Abstracts of the 28th Annual Meeting of the Society for Neuroscience 24 620 (No.244.14), 1998. (A)